title: IL12RB2 and ABCA1 genes are associated with susceptibility to radiation dermatitis.
abstract: OBJECTIVE
  Severe acute radiation dermatitis is observed in approximately 5% to 10% of patients who receive whole-breast radiotherapy. Several factors, including treatment-related and patient-oriented factors, are involved in susceptibility to severe dermatitis. Genetic factors are also thought to be related to a patient's susceptibility to severe dermatitis. To elucidate genetic polymorphisms associated with a susceptibility to radiation-induced dermatitis, a large-scale single-nucleotide polymorphism (SNP) analysis using DNA samples from 156 patients with breast cancer was conducted.
  
  
  METHODS
  Patients were selected from more than 3,000 female patients with early breast cancer who received radiotherapy after undergoing breast-conserving surgery. The dermatitis group was defined as patients who developed dermatitis at a National Cancer Institute Common Toxicity Criteria grade of > or =2. For the SNP analysis, DNA samples from each patient were subjected to the genotyping of 3,144 SNPs covering 494 genes.
  
  
  RESULTS
  SNPs that mapped to two genes, ABCA1 and IL12RB2, were associated with radiation-induced dermatitis. In the ABCA1 gene, one of these SNPs was a nonsynonymous coding SNP causing R219K (P = 0.0065). As for the IL12RB2 gene, the strongest association was observed at SNP-K (rs3790568; P = 0.0013). Using polymorphisms of both genes, the probability of severe dermatitis was estimated for each combination of genotypes. These analyses showed that individuals carrying a combination of genotypes accounting for 14.7% of the Japanese population have the highest probability of developing radiation-induced dermatitis.
  
  
  CONCLUSIONS
  Our results shed light on the mechanisms responsible for radiation-induced dermatitis. These results may also contribute to the individualization of radiotherapy.
authors.affiliation: Genome Center, Japanese Foundation for Cancer Research, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Isomura
authors.forename: Natsuo
authors.initials: N
authors.lastname: Oya
authors.forename: Seiji
authors.initials: S
authors.lastname: Tachiiri
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kaneyasu
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Akimoto
authors.forename: Masato
authors.initials: M
authors.lastname: Hareyama
authors.forename: Tadasi
authors.initials: T
authors.lastname: Sugita
authors.forename: Norio
authors.initials: N
authors.lastname: Mitsuhashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamashita
authors.forename: Masahiko
authors.initials: M
authors.lastname: Aoki
authors.forename: Heitetsu
authors.initials: H
authors.lastname: Sai
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hirokawa
authors.forename: Koh-Ichi
authors.initials: K
authors.lastname: Sakata
authors.forename: Kumiko
authors.initials: K
authors.lastname: Karasawa
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tomida
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuruo
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Miki
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Noda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiraoka
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000150:complications* / Q000235:genetics* / Q000532:radiotherapy; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011855:Radiodermatitis / Q000235:genetics* / Q000532:radiotherapy; D053707:Receptors, Interleukin-12 / Q000235:genetics*; D012307:Risk Factors
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; C508439:IL12RB2 protein, human; D053707:Receptors, Interleukin-12